The present invention relates to a supported osmate useful as a reusable catalyst in the preparation of vicinal diols. The present invention also relates to a process for the preparation of supported osmates of the formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules and use thereof in the preparation of vicinal diols by asymmetric dihydroxylation (AD) of olefins in presence of cinchona alkaloid compounds.
Asymmetric dihydroxylation of olefins in the presence of cinchona alkaloid results in products that are important intermediates in the preparation of various drugs and chemicals. For example, the products of cinnamic acid esters are intermediates for taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antibiotic. Proranolol, a xcex2 blocker can also be derived from diols obtained through this method.
There are serious disadvantages in performing the catalytic AD reaction with homogeneous system in the manufacture of vicinal diols due to presence of toxic remnants of osmium in products and high cost of osmium tetraoxide or potassium osmate dihydrate. By employing the heterogeneous catalytic system, the cost naturally comes down due to easy recovery of the catalyst and very insignificant loss of osmium tetraoxide, when compared with homogeneous system. The products thus obtained using heterogeneous catalyst system are benign in the sense that the presence of osmium in minor impurities in the dihydroxylated products is also precluded.
U.S. Pat. Nos. 4,871,855 and 5,260,421 disclose processes for asymmetric dihydroxylation of olefins using osmium tetraoxide and cinchona alkaloids using homogenous catalyst systems. These processes involve cumbersome recovery of the osmium catalyst from the reaction mixture, generation of toxic waste and the potential presence of toxic osmium in the product.
U.S. Pat. Nos. 5,516,929 and 5,260,461 disclose asymmetric dihydroxylation of olefins using osmium tetraoxide and polymer bound cinchona alkaloids in a heterogeneous system. The quantitative recovery of the toxic osmium catalyst, lower enantioselectivity and reduction in activity and enantioselectivity in each recycle experiments are some of the disadvantages associated with this process.
U.S. Pat. No. 5,968,867 discloses asymmetric dihydroxylation of olefins using osmium tetraoxide and silica gel supported bis-cinchona alkaloid derivatives in a heterogeneous system. Quantitative recovery of toxic osmium catalyst is difficult and a reduction in activity and enantioselectivity of the catalyst is observed in each and every recycle experiment.
European Patent 940,170 A2 describes the catalytic asymmetric dihydroxylation of alkenes using a polymer supported osmium catalyst. The drawbacks of this process are that higher amounts of catalyst are required (5 mol %), the reaction time is very long and expensive polymers are used as supports.
The main object of the invention is to provide a heterogeneous recyclable supported osmate of the general formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules and use thereof in the preparation of vicinal diols by asymmetric dihydroxylation (AD) of olefins in presence of cinchona alkaloid compounds.
It is another object of the invention to provide a process for the preparation of a novel heterogeneous recyclable supported osmate of the general formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules and use thereof in the preparation of vicinal diols.
It is another object of the invention to provide a environmentally friendly process for the asymmetric dihydroxylation of olefins to obtain vicinal diols using a novel heterogeneous supported osmate of the invention.
It is a further object of the invention to provide a process for the preparation of vicinal diols with good enantioselectivity, activity and yield by the asymmetric dihydroxylation of olefins using a novel osmate catalyst of the invention.
It is yet another object of the invention to provide a process for the preparation of vicinal diols by the asymmetric dihydroxylation of olefins in the presence of cinchona alkaloids and derivatives thereof, which process is simple, economical and results in a product with no traces of toxic osmium therein.
It is a further object of the invention to provide a process for the preparation of vicinal diols by the asymmetric dihydroxylation of olefins in the presence of cinchona alkaloids and derivatives thereof wherein the catalyst is capable of recycle several times without substantial loss of activity or in yield of product.
These and other objects of the invention are achieved by using the novel supported heterogeneous osmate catalyst of the general formula Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules for the asymmetric dihydroxylation of olefins in the presence of cinchona alkaloids to obtain vicinal diols with good yield and selectivity.
The novelty of the invention lies in the supported osmate catalyst and in preparation of vicinal diols in presence of cinchona alkaloids or derivatives employing oxidants.
Accordingly, the present invention provides a supported osmate of the general formula Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules.
In one embodiment of the invention, the support is selected from resin and silica.
In another embodiment of the invention, R is selected from methyl, ethyl, propyl, butyl and like alkyl groups.
In a further embodiment of the invention, the osmium content in the catalyst is in the range of 1 to 30%.
In a further embodiment of the invention, the support S as synthesized has charge balancing anions selected from chloride, bromide, iodide, fluoride, hydroxide and acetate.
The invention also relates to a process for the preparation of a novel heterogeneous supported osmate catalyst of the formula Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules, said process comprising reacting potassium osmate with a quaternary ammonium species in water.
In one embodiment of the invention, the potassium osmate is of the formula K2OsO42H2O.
In another embodiment of the invention, the quaternary ammonium species is of the formula Sxe2x80x94NR3X wherein S is a support, R is alkyl, and X is selected from Cl, Br, I, F, xe2x80x94OH and OAc.
In a further embodiment of the invention, the reaction is carried out at a temperature in the range of 25 to 100xc2x0 C. for a period in the range of 5-24 hours.
In one embodiment of the invention, the osmium content in the catalyst is in the range of 1 to 30%.
In another embodiment of the invention, the support S is selected from resin and silica.
In a further embodiment of the invention, the support S as synthesized has charge balancing anions selected from chloride, bromide, iodide, fluoride, hydroxide and acetate.
In another embodiment of the invention, R is selected from methyl, ethyl, propyl, butyl and like alkyl groups.
The present invention also provides a process for the preparation of vicinal diols comprising asymmetrically dihydroxylating the corresponding olefin in the presence of a cinchona alkaloid using an oxidant in a solvent selected from the group consisting of water, acetone, acetonitrile, t-butanol and any mixture thereof, at a temperature in the range of xe2x88x9270 to 100xc2x0 C. for a period in the range of 0.5 to 24 hours, and in the presence of a catalytic amount of a heterogeneous supported osmate catalyst of the general formula Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules, and recovering the pure vicinal diol.
In one embodiment of the invention, the osmium content in the catalyst is in the range of 1 to 30%.
In another embodiment of the invention, the support S is selected from resin and silica.
In a further embodiment of the invention, the support S used has charge balancing anions selected from chloride, bromide, iodide, fluoride, hydroxide and acetate.
In another embodiment of the invention, R is selected from methyl, ethyl, propyl, butyl and like alkyl groups.
In yet another embodiment of the invention, the amount of supported osmate used in the reaction is 0.01 to 10 mol % of osmium content with respect to the substrate.
In yet another embodiment of the invention the solvent used comprises a solvent system selected from the group consisting of water:acetone, water:acetonitrile and water:t-butanol, the ratio of water to acetone, acetonitrile and t-butanol being in the range of 1:1 to 1:3, and water:acetone:acetonitrile in a ratio of 1:1:1.
In another embodiment of the invention, the catalyst is recovered from the reaction system and recycled to the reaction system as many times as desired.
In a further embodiment of the invention, the oxidant used is selected from the group consisting of N-methylmorpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen.
In yet another embodiment of the invention, the cinchona alkaloid and derivatives thereof comprise a monomeric and polymeric chiral ligand.
In a further embodiment of the invention, the chiral ligand is selected from the group consisting of (DHQD)2PHAL, (DHQD)2PYR, (DHQD)2AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and pseudoenantiomeric forms thereof.
The novelty of the invention lies in the supported osmate catalyst and in preparation of vicinal diols in the presence of cinchona alkaloids or derivatives employing oxidants.
The novel supported osmate is of the general formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules. The support is preferably selected from resin or silica. R is preferably selected from methyl, ethyl, propyl, butyl and like alkyl groups. The osmium content in the catalyst is generally in the range of 1 to 30%. The support S as synthesized may contain charge balancing anions selected from chloride, bromide, iodide, fluoride, hydroxide and acetate.
The heterogeneous osmate catalyst of the general formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules is prepared by reacting potassium osmate with supported quaternary ammonium species in water as a solvent at a temperature in the range of 25 to 100xc2x0 C. for a period in the range of 5-24 hours to obtain the desired catalyst.
The process for preparation of vicinal diols comprises asymmetrically dihydroxylating the corresponding olefin in the presence of a cinchona alkaloid compound using an oxidant in a solvent selected from the group consisting of water, acetone, acetonitrile, t-butanol and any mixture thereof, at a temperature in the range of xe2x88x9270 to 100xc2x0 C. for a period in the range of 0.5 to 24 hours, and in the presence of a catalytic amount of a heterogeneous supported osmate catalyst of the general formula (Sxe2x80x94NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules, and recovering the pure vicinal diol by any conventional method. The amount of supported osmate used in the reaction is 0.01 to 10 mol % of osmium content with respect to the substrate.
The catalyst can be recovered from the reaction system by any conventional process and recycled to the reaction system several times without any substantial loss of activity or of yield of the product. The oxidant used is selected from N-methylmorpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen. The cinchona alkaloid and derivatives thereof comprise a monomeric and polymeric chiral ligand such as for example (DHQD)2PHAL, (DHQD)2PYR, (DHQD)2AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and pseudoenantiomeric forms thereof.
Scientific Explanation
In the present invention, novel supported osmates were prepared for the first time using the anion exchange method from the supported quaternary ammonium species. The osmate anions present on the support are responsible for the dihydroxylation activity of the reaction. The activity of the supported osmate is similar or higher than the homogeneous counterparts. Without wishing to be bound by any theory, it is believed that the higher activity is ascribed to the support effect. The large positive potential of OsO42xe2x88x92 support surface induces polarisation of Nxe2x86x92O bond and facilitates oxygen transfer.
Higher yields and enantioselectivities are obtained with supported osmate catalysts used in the asymmetric dihydroxylation of olefins in aqueous organic solvents. Since the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals, this invention is timely and appropriate. Therefore, supported osmate is a better option for the synthesis of vicinol diols. The supported osmate catalysts prepared from various supports offered good yields and enantioselectivies in presence of cinchona alkaloids. Thus this invention offers the best techno-economic route for the synthesis of vicinol diols, intermediates for the preparation of drugs and pharmaceuticals.
Supported osmates are prepared as exemplified and used in catalytic amounts for preparing vicinol diols by asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds in a heterogeneous manner as described.
The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the invention.
Preparation of Catalysts